Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells

Serotonin (5-hydroxytryptamine, or 5-HT), released from activated platelets , not only accelerates aggregation of platelets but also is known to promot e mitosis, migration, and contraction of vascular smooth muscle cells (VSMC s). These effects are considered to contribute to thrombus formation and at herosclerosis. The aim of this study was to investigate the effects of 5-HT on the expressions of coagulative and fibrinolytic factors in rat aortic e ndothelial cells. Endothelial cells were stimulated with various concentrat ions of 5-HT (0.1 similar to 10 muM), and the expressions of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibit or-1 (PAI-1), and tissue-type plasminogen activator (TPA) messenger RNAs (m RNAs) were evaluated by Northern blot analysis. The activities of TF and PA I-1 were also measured. TF and PAI-1 mRNA were increased significantly in a concentration- and time-dependent manner. However, TFPI and TPA mRNA expre ssion did not change. The inductions of TF and PAI-1 mRNAs were inhibited b y a 5-HT1/5-HT2 receptor antagonist (methiothepin) and a selective 5-HT2A r eceptor antagonist (MCI-9042). These results indicate that 5-HT increases p rocoagulant activity and reduces fibrinolytic activities of endothelial cel ls through the 5-HT2A receptor. It was concluded that the modulation of pro coagulant and hypofibrinolytic activities of endothelial cells by 5-HT syne rgistically promotes thrombus formation at the site of vessel injury with t he platelet aggregation, VSMC contraction, and VSMC proliferation. (Blood. 2001; 97:1697-1702) (C) 2001 by The American Society of Hematology.